Yale Research Articles

Follow the Trace: Becoming a Seismo-Detective with a Campus-Based Raspberry Shake Seismometer

Abstract Seismic signals, whether caused by earthquakes, other natural phenomena, or artificial noise sources, have specific characteristics in the time and frequency domains that contain crucial information reflecting their source. The analysis of seismic time series is an essential part of every seismology-oriented study program. Enabling students to work with data collected from their own campus, including signals from both anthropogenic and natural seismic sources, can provide vivid, practical examples to make abstract concepts communicated in classes more concrete and relevant. Data from research-grade broadband seismometers enable us to record time series of vibrations at a broad range of frequencies; however, these sensors are costly and are often deployed in remote places. Participation in the Raspberry Shake citizen science network enables seismology educators to record seismic signals on our own campuses and use these recordings in our classrooms and for public outreach. Yale University installed a Raspberry Shake three-component, low-cost seismometer in the Earth and Planetary Sciences department building in Summer 2022, enabling the detection of local, regional, and teleseismic earthquakes, microseismic noise, and anthropogenic noise sources from building construction, an explosive event in a steam tunnel, and general building use. Here, we discuss and illustrate the use of data from our Raspberry Shake in outreach and education activities at Yale. In particular, we highlight a series of ObsPy-based exercises that will be used in courses taught in our department, including our upper-level Introduction to Seismology course and our undergraduate classes on Natural Disasters and Forensic Geoscience.

Visual analysis of trustworthiness studies: based on the Web of Science database

Trustworthiness is the most significant predictor of trust and has a significant impact on people’s levels of trust. Most trustworthiness–related research is empirical, and while it has a long history, it is challenging for academics to get insights that are applicable to their fields of study and to successfully transfer fragmented results into practice. In order to grasp their dynamic development processes through the mapping of network knowledge graphs, this paper is based on the Web of Science database and uses CiteSpace (6.2.R4) software to compile and visualize the 1,463 publications on trustworthy studies over the past 10 years. This paper aims to provide valuable references to theoretical research and the practice of Trustworthiness. The findings demonstrate that: over the past 10 years, trustworthiness-related research has generally increased in volume; trustworthiness research is concentrated in industrialized Europe and America, with American research findings having a bigger global impact; The University of California System, Harvard University, and Yale University are among the high-production institutions; the leading figures are represented by Alexander Todorov, Marco Brambilla, Bastian Jaeger, and others; the core authors are distinguished university scholars; however, the level of cooperation of the core author needs to be improved. The primary journal for publishing research on trustworthiness is the Journal of Personality and Social Psychology and Biology Letters. In addition, the study focuses on three distinct domains, involving social perception, facial clues, and artificial intelligence.

The rise and fall of the east: how exams, autocracy, stability, and technology brought china success, and why they might lead to its decline. Yasheng huang. New Haven, Yale University Press, 2023, 440 pages

The rise and fall of the east: how exams, autocracy, stability, and technology brought china success, and why they might lead to its decline. Yasheng huang. New Haven, Yale University Press, 2023, 440 pages

Kuliner “Timlo Solo” sebagai Bahan Ajar BIPA dalam Upaya Internasionalisasi Bahasa Indonesia

This article discusses the important role of teaching the Indonesian language for Foreign Speakers (BIPA) in supporting the internationalization of the language of Indonesia, with a focus on the use of the culinary material "Timlo Solo" in learning BIPA at Yale University. Through a qualitative method with a literature study approach, the study reviews the history, variation, way of making, culinary location, and role in Timlo Solo's local culinarian culture. The results of the study show that the use of Timlo solo's cooking lessons helps foreign students understand not only language, but also the cultural context, social life, and norms in Indonesia. By using culinary as a teaching material, BIPA students can gain a deeper understanding of Indonesian cultural diversity. In addition, the culinary integration in BIPA learning enriches the learning experience with practical and enjoyable aspects. In the context of the internationalization of the Indonesian language, the use of Timlo Solo’s culinary lessons at Yale University is a significant step in broadening the understanding and appreciation of Indonesia’s culture among foreign students.

Abstract PO4-15-03: Quantitative Measurement of TROP2 via Chromogenic Immunohistochemistry in Breast Cancer

Abstract Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets human trophoblast cell-surface antigen 2 (TROP2), which is expressed in over 90% of breast cancer cases (Zaman et al, 2019). By delivering the cytotoxic SN-38 (topoisomerase I inhibitor) to TROP2 expressing breast cancer cells, SG showed promising antitumor activities in clinical trials and is now an approved treatment for triple-negative breast cancer (TNBC) and hormone receptor (HR)-positive HER2-negative breast cancer in the metastatic setting. Despite the prevalent expression of TROP2 in breast cancer, the objective response rates reported from clinical trials were about 30%, indicating the need for a diagnostic test that can identify which patients are likely to benefit from therapy. Although the drug is approved without a companion diagnostic assay, recent data from the TROPiCS-02 trial has shown that TROP2-low (H-score < 100) showed a non-significant hazard ratio for benefit from SG. In the same study, patients treated with SG with H-score >100 showed a significant hazard ratio for benefit compared to physician’s choice (Tolaney et al, ASCO 2023). This suggests that TROP2 expression level is associated with SG response and that a threshold for TROP2 expression level may aid patient selection. Although over 90% of breast cancer patients were considered TROP2-positive by IHC, the expression level of TROP2 was never quantitatively assessed in large breast cancer cohorts. Here we describe a quantitative chromogenic immunohistochemistry (IHC) assay with a cell line standard. Mass spectrometry was used to measure TROP2 peptide concentrations in the six standard cell lines, and the correlation between the mass spectrometry and IHC data for each cell line was then used to convert chromogenic signals to concentrations of TROP2 protein (fmol/mm2). The antibody used in this assay was rigorously validated, and the antibody concentration was optimized for the best signal-to-noise ratio. The optical density (OD) of chromogenic staining was measured using QuPath 0.4.3 (Qymia extension) by identifying the tumor area via object classifiers and manual editing and then calculating the area-normalized sum of OD. Collectively, this assay can measure up to 29.1 fmol/mm2 of TROP2. By applying this assay to two serial retrospective primary breast cancer cohorts from Yale University, we quantitatively measured TROP2 expression levels in 332 clinical cases. Not surprisingly, over 90% of cases showed some chromogenic signal, with a median TROP2 concentration of 2.1 fmol/mm2 and a maximum of 10.5 fmol/mm2. TROP2 expression levels showed no significant association with clinicopathologic characteristics including race, stage, BRCA mutation status, molecular subtype, HER2 IHC levels, and outcome. Further work is underway to optimize the assay toward the goal of determination of whether there is a quantitatively definable threshold for TROP2 expression below which patients are unlikely to benefit from SG or other TROP2-targeted therapies. Citation Format: Mengni He, Matthew Liu, Thazin Aung, Sneha Burela, Katherine Bates, Charles Robbins, David Rimm. Quantitative Measurement of TROP2 via Chromogenic Immunohistochemistry in Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-03.

Abstract PO3-13-11: Quantitative Multiplex Immunofluorescence Assay for TROP2 and HER2 Expression in Breast Cancer: Towards Guiding Patient Selection for Antibody Drug Conjugate Therapies

Abstract Emerging antibody drug conjugate (ADC) therapies targeting human trophoblast cell-surface antigen (TROP2) and human epidermal growth factor receptor 2 (HER2) are transforming the treatment landscape for breast cancer. Sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have gained approval for an overlapping set of "HER2-low" metastatic breast cancers, including hormone receptor (HR)-positive HER2 non-amplified and "triple-negative" subtypes. Nevertheless, the optimal selection of patients and treatment sequencing for these ADC therapies remains a clinical challenge. Clinical trial objective response rates to SG are approximately 30%, compared to 30-90% for T-DXd depending on HER2 expression levels. While both drugs are thought to be targeted therapies, the value of measuring the target and the best methods to do so are still not established. We believe that quantitative measurement of TROP2 and HER2 antigen expression levels could establish thresholds for responders, enabling more effective patient selection for ADC therapies. Here, we present a TROP2, high-sensitivity HER2, and cytokeratin (CK) quantitative immunofluorescence (QIF) multiplex assay. Using a ten-cell line standard array and proteomic mass spectrometry, we can convert tumor compartment QIF intensity to protein concentration in fmol/mm2 for tissue specimens. Anti-HER2, anti-TROP2 antibodies, and fluorescence detection systems were titrated and combined to maximize signal-to-noise ratio on our cell line standard array and breast cancer tissue microarrays (TMA). The multiplex assay was designed for automated slide stainers (Leica BOND Rx) and fluorescence slide scanning (Rarecyte CyteFinder II HT). We perform our analyses in QuPath using an image processing plugin developed for automated QIF/IHC analysis (Qymia). Reproducible TROP2 and HER2 QIF scoring (R² > 0.95) was achieved across multiple staining batches using serial sections of breast cancer TMAs and cell standard arrays. This assay has a TROP2 linear range between 0.63 - 9.17 fmol/mm2 (about 1 million TROP2 receptors/cell) and HER2 linear range between 0.09 - 0.565 fmol/mm2 (about 60,000 HER2 receptors/cell). We then applied this multiplex assay to two serial retrospective primary breast cancer cohorts from Yale University to quantitatively measure TROP2 and HER2 expression (338 clinical cases). We find a weak negative correlation between TROP2 and HER2 expression in our breast cancer cohorts (Pearson r = -0.14, p = 0.0097, n = 338). TROP2 expression levels were above the limit of detection (LOD) in 90.2% of cases, with 4.1% exceeding the limit of linearity (LOL), and a mean TROP2 expression of 4.05 fmol/mm2. For HER2, 67.2% of cases were above the LOD, with 7.1% exceeding the LOL, and a mean HER2 expression of 0.186 fmol/mm2. Both TROP2 and HER2 were below the LOD in 3.0% of cases, which we define as “negative”. We found 29.9% expressed TROP2 and were HER2-negative, and 6.8% expressed HER2 and were TROP2-negative. Our future studies will aim to quantitatively define expression thresholds for T-DXd and SG response with the goal to produce a clinical grade assay for ADC patient selection and determine the value of the assay to help select which ADC to give first. HER2 and TROP2 protein expression summary in Yale breast cancer cohort Table 1: Summary of HER2 and TROP2 protein expression levels in serial retrospective primary breast cancer cohort of 338 cases using our high-sensitivity HER2 and TROP2 multiplex immunofluorescent assay Citation Format: Charles Robbins, Mengni He, Revekka Khaimova, Katherine Bates, Nay Nwe Nyein Chan, Daniel Liebler, Regan Fulton, David Rimm. Quantitative Multiplex Immunofluorescence Assay for TROP2 and HER2 Expression in Breast Cancer: Towards Guiding Patient Selection for Antibody Drug Conjugate Therapies [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-11.

Unlocking Diversity in Cardiovascular Clinical Research: Lessons from the Screening for Cardiac Amyloidosis With Nuclear Imaging in a Minority Populations Study

The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations study seeks to determine the prevalence of transthyretin cardiac amyloidosis (ATTR-CA) among older Black or Caribbean Hispanic individuals with heart failure and an increased wall thickness. We noticed varied recruitment percentages across the recruiting sites and sought to determine the factors associated with greater percentage enrollment of eligible participants. The percentage of enrolled to eligible participants was calculated across study sites. Baseline demographic and clinical characteristics, health literacy, trust in providers, perceived discrimination, area deprivation index (ADI) and English proficiency were compared by site using Kruskal-Wallis's test or one-way ANOVA for continuous variables and the Chi-Square test or Fisher's exact test for categorical variables. Wilcoxon rank sum and Chi-Square tests, with multiple comparisons correction using the false discovery rate (FDR) method, were used as post-hoc analysis when results were statistically significant. Among the four recruiting sites, Boston Medical Center, Columbia University Irving Medical Center, Harlem Hospital and Yale University, which employed different recruitment approaches, the percentage of participants enrolled among eligible participants differed, with the highest rate at Harlem Hospital (n=149 of 310, 48%), followed by Yale University (n=27 of 67, 40%), Boston University (n=247 of 655, 38%), and Columbia University (n=137of 442, 32%), p <0.01. Direct recruitment by the primary cardiovascular care team providing clinical care was associated with higher percent enrolled across sites as were higher education levels and English proficiency. Enrollment differences across sites were not associated with the number of chronic diseases, physician trust, perceived discrimination, or health literacy. Recruitment of eligible under-represented minorities (URMs) in SCAN-MP was associated with approaches employed in recruitment, including direct initial contact by the primary cardiovascular care team providing the potential participant's clinical care. Such data may help improve approaches to more successful recruitment of URMs in clinical research.

Narrative triggers of information sensitivity

This research explores the factors contributing to information sensitivity in debt markets, focusing on the potential influences of uncertainty, economic performance, and journalist-dependent language. Building upon the foundational work of Dang et al. (Ignorance, debt and financial crises. Yale University Unpublished Working Paper, 2018), we analyze the mechanisms underlying the transition from information-insensitive to information-sensitive states—a shift with implications for potential financial crises. Leveraging machine learning techniques and daily data on variables such as default probability, information acquisition, and newspaper articles, we discern specific narrative triggers embedded within the news. Our analysis underscores the pivotal role of economic states and journalist language in inducing information sensitivity—a phenomenon intricately tied to different psychological thinking processes.

Methods of Modelling Electronic Academic Libraries: Technological Concept of Electronic Libraries

Abstract The relevance of examining modelling methods in academic electronic libraries is justified by the need to understand the library’s structure and ensure its operation in technological terms. The purpose of this study is to analyse the applied modelling methods for electronic libraries serving Kazakhstani and international higher education institutions. The study employed basic (structural, comparative-comparative) and additional (analytical-synthetic, graphical) methods. During this study, it was found that the main modelling methods for modern electronic libraries include the following: conceptual with the establishment of a clear hierarchy between objects of the electronic library and attributes of search queries, logical using search categorisation, informational employing the semantic principle of material construction and systemic-functional ensuring a balance between functions, structure, technologies and the management system. In particular, after modelling the structure of Kazakhstani, British and American digital libraries at universities, it was determined that the Yale University Electronic Library Collection is built on the method of logical modelling, the Electronic Library at L.N. Gumilyov Eurasian National University uses the systemic-functional method, the Cambridge University Electronic Library employs the informational method and the Al-Farabi Library uses the conceptual method.

The 2024 IUPAC-Richter Award Goes to Craig M. Crews

Abstract Craig M. Crews has been awarded the 2024 IUPAC-Richter Prize in Medicinal Chemistry. Crews is a Professor in the Department of Molecular, Cellular and Developmental Biology and Professor of Chemistry and Pharmacology at Yale University. His discovery and implementation of the PROteolysis TArgeting Chimeras (PROTACs) technology for removing specific unwanted proteins revolutionized the field by identifying a new method for affecting protein function. The fact that this technology has been widely adapted and investigated not only within the pharmaceutical industry, but also in academia, demonstrates the significance and impact of this work. While no drugs have yet been approved, several are in development and these molecules are progressing, because they are effective and safe. He also played a key role in the discovery of carfilzomib, an approved proteasome inhibitor for the treatment of multiple myeloma. The acceptance lecture will be held in Rome, Italy (1-5 September 2024) at the XXVIII EFMC International Symposium on Medicinal Chemistry.

I Give These Books: The History of Yale University Library 1656–2022, by David Alan Richards

<i>I Give These Books: The History of Yale University Library 1656–2022</i>, by David Alan Richards

John Brewer, Volcanic. Vesuvius in the Age of Revolutions. London, Yale University Press 2023

John Brewer, Volcanic. Vesuvius in the Age of Revolutions. London, Yale University Press 2023

Memory and Labor History in Modern Chile - Ránquil: Rural Rebellion, Political Violence, and Historical Memory in Chile. By Thomas Miller Klubock. New Haven: Yale University Press, 2022. Pp. 288. $50.00 cloth.

Memory and Labor History in Modern Chile - Ránquil: Rural Rebellion, Political Violence, and Historical Memory in Chile. By Thomas Miller Klubock. New Haven: Yale University Press, 2022. Pp. 288. $50.00 cloth.

A Study of Global Trade War and Its Impact on Indian Economy

A Study of Global Trade War and Its Impact on Indian Economy

Current global status of male reproductive health.

Current global status of male reproductive health.

Combating the myth of “innate genius” in science

In this Stories piece, Sigrid Nachtergaele-an assistant professor at the Yale University Department of Molecular, Cellular, and Developmental Biology-shares her experience and efforts to cut barriers for the next generation of aspiring scientists.

Pesellino: A Renaissance Master Revealed (London, The National Gallery, 7 December 2023 –10 March 2024). Catalogue by Laura Llewellyn (ed.), with contributions by Jill Dunkerton and Nathaniel Silver. London: National Gallery Global Limited, distributed by Yale University Press, 2023. 80 pp., illus. col., ISBN 97818570971081052658.

Pesellino: A Renaissance Master Revealed (London, The National Gallery, 7 December 2023 –10 March 2024). Catalogue by Laura Llewellyn (ed.), with contributions by Jill Dunkerton and Nathaniel Silver. London: National Gallery Global Limited, distributed by Yale University Press, 2023. 80 pp., illus. col., ISBN 97818570971081052658.

Implementation of Chatbot Technology in Health Care: Protocol for a Bibliometric Analysis.

Chatbots have the potential to increase people's access to quality health care. However, the implementation of chatbot technology in the health care system is unclear due to the scarce analysis of publications on the adoption of chatbot in health and medical settings. This paper presents a protocol of a bibliometric analysis aimed at offering the public insights into the current state and emerging trends in research related to the use of chatbot technology for promoting health. In this bibliometric analysis, we will select published papers from the databases of CINAHL, IEEE Xplore, PubMed, Scopus, and Web of Science that pertain to chatbot technology and its applications in health care. Our search strategy includes keywords such as "chatbot," "virtual agent," "virtual assistant," "conversational agent," "conversational AI," "interactive agent," "health," and "healthcare." Five researchers who are AI engineers and clinicians will independently review the titles and abstracts of selected papers to determine their eligibility for a full-text review. The corresponding author (ZN) will serve as a mediator to address any discrepancies and disputes among the 5 reviewers. Our analysis will encompass various publication patterns of chatbot research, including the number of annual publications, their geographic or institutional distribution, and the number of annual grants supporting chatbot research, and further summarize the methodologies used in the development of health-related chatbots, along with their features and applications in health care settings. Software tool VOSViewer (version 1.6.19; Leiden University) will be used to construct and visualize bibliometric networks. The preparation for the bibliometric analysis began on December 3, 2021, when the research team started the process of familiarizing themselves with the software tools that may be used in this analysis, VOSViewer and CiteSpace, during which they consulted 3 librarians at the Yale University regarding search terms and tentative results. Tentative searches on the aforementioned databases yielded a total of 2340 papers. The official search phase started on July 27, 2023. Our goal is to complete the screening of papers and the analysis by February 15, 2024. Artificial intelligence chatbots, such as ChatGPT (OpenAI Inc), have sparked numerous discussions within the health care industry regarding their impact on human health. Chatbot technology holds substantial promise for advancing health care systems worldwide. However, developing a sophisticated chatbot capable of precise interaction with health care consumers, delivering personalized care, and providing accurate health-related information and knowledge remain considerable challenges. This bibliometric analysis seeks to fill the knowledge gap in the existing literature on health-related chatbots, entailing their applications, the software used in their development, and their preferred functionalities among users. PRR1-10.2196/54349.

The impact of interviewer characteristics on residency candidate scores in Emergency Medicine: a brief report.

At the conclusion of residency candidate interview days, faculty interviewers commonly meet as a group to reach conclusions about candidate evaluations based on shared information. These conclusions ultimately translate into rank list position for The Residency Match. The primary objective is to determine if the post-interview discussion influences the final scores assigned by each interviewer, and to investigate whether interviewer characteristics are significantly associated with the likelihood of changing their score. Based on Foucault's 'theory of discourse' and Bourdieu's 'social capital theory,' we hypothesized that interviewer characteristics, and the discourse itself, would contribute to score changes after a post-interview discussion regarding emergency medicine residency candidates. We conducted a cross-sectional observational study of candidate scores for all candidates to a four-year emergency medicine residency program affiliated with Yale University School of Medicine during a single application cycle. The magnitude and direction of score changes, if any, after group discussion were plotted and grouped by interviewer academic rank. We created a logistic regression model to determine the odds that candidate scores changed from pre- and post-discussion ratings related to specific interviewer factors. A total of 24 interviewers and 211 candidates created 471 unique interviewer-candidate scoring interactions, with 216 (45.8%) changing post-discussion. All interviewers ranked junior to professor were significantly more likely to change their score compared to professors. Interviewers who were women had significantly lower odds of changing their individual scores following group discussion (p=0.020; OR 0.49, 95% CI 0.26-0.89). Interviewers with lower academic rank had higher odds of changing their post-discussion scores of residency candidates compared to professors. Future work is needed to further characterize the influencing factors and could help create more equitable decision processes during the residency candidate ranking process.

Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University

Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d’Hérelle’s first publication on the clinical applications of phages. At the Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established to offer safe and potent phages for single-patient investigational new drug applications while recognizing the time constraints imposed by infection(s). This study provides a practical walkthrough of the pipeline with an Autographiviridae phage targeting Pseudomonas aeruginosa (phage vB_PaeA_SB, abbreviated to ΦSB). Notably, a thorough phage characterization and the evolutionary selection pressure exerted on bacteria by phages, analogous to antibiotics, are incorporated into the pipeline.